Cyclacel Pharmaceuticals, Inc. reported preliminary dose escalation data from its ongoing 065-101 Phase 1/2 clinical study of oral fadraciclib, a cyclin dependent kinase (CDK) 2/9 inhibitor, for the treatment of patients with advanced solid tumors and lymphoma. Of the 18 patients evaluable for response, two out of three T cell lymphoma patients treated achieved partial response and 11 out of 15 patients with various solid tumors achieved stable disease. No dose-limiting toxicities have been observed thus far.

Data were presented during a poster presentation at the 34th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics, which is being held on October 26-28, in Barcelona, Spain. Summary of findings: · As of September 30, 2022, 18 evaluable patients were treated with oral fadraciclib as a single agent. Patients were heavily pretreated with various tumor types, including breast, cholangiocarcinoma, gynecological, head & neck, hepatocellular carcinoma, T-cell lymphoma, pancreatic and prostate cancers.

Fadraciclib was well tolerated while escalating from dose levels 1 to 5 (up to and including 100mg BID, Monday-Friday, on week 1-4 in 28-day cycles). No treatment-related Serious Adverse Events (SAEs), or SUSAR, or Dose-Limiting Toxicities (DLTs) were reported. Initial anticancer activity was as follows: · Two partial responses (PRs) have been observed in T-cell lymphoma patients, one with CTCL and one with angioimmunoblastic PTCL.

Four patients (with cervical, endometrial, HCC, and ovarian cancers) achieved target lesion reductions. A patient with pancreatic cancer achieved stable disease for 5 cycles. Plasma concentration of fadraciclib is dose proportional, crossing the target engagement threshold level for CDK2 and CDK9 with increasing duration at dose levels 4 and 5 after repeated oral administration.

Enrollment continues at dose level 6 (150mg BID, Monday-Friday, on week 1-4 in 28-day cycles). The ongoing trial is an open-label, multicenter, Phase 1/2 study in adult subjects with advanced solid tumors and lymphoma. Phase 1 explores both schedule and escalating doses of oral fadraciclib as a single-agent in 28-day cycles with a primary objective of identifying maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

Once RP2D is established, Phase 2 will enroll patients in seven specific tumor-type groups and a basket cohort, utilizing a Simon two-stage optimal design to evaluate clinical activity. The primary objective of Phase 2 is to achieve proof of concept and determine preliminary efficacy by overall response rate. Safety, pharmacokinetics (PK) and efficacy will be investigated for all subjects.

Exploratory objectives are to investigate clinical pharmacodynamics (PD) and pharmacogenomics (PGx) of fadraciclib.